Clinical Review

A Review of Neurologic Complications of Biologic Therapy in Plaque Psoriasis

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The use of biologic medications has represented a great advancement in the treatment of moderate to severe plaque psoriasis and has improved patients’ quality of life. Despite the increasing popularity of biologics, their neurological side effects have been a constant concern. Reports of demyelinating diseases associated with tumor necrosis factor α (TNF-α) inhibitors continue to accumulate. Additionally, efalizumab was withdrawn from the market in 2009 for causing progressive multifocal leukoencephalopathy (PML). These reports highlight the need for dermatologists to inform patients of the risks and promote informed decision-making with patients prior to starting a biologic agent. Dermatologists also need to recognize early manifestations of neurologic side effects. This review provides an overview of the literature on neurologic diseases that have been found to be associated with biologic agents used for plaque psoriasis. Clinical presentations and diagnostic workups of such diseases are given to aid dermatologists in their early diagnosis and referral.

Practice Points

  • Patients with a personal or strong family history of demyelinating disease should be considered for alternative treatment options before initiating anti–tumor necrosis factor (TNF) α therapy.
  • Patients on biologic agents, especially TNF-α inhibitors, with subacute or rapidly progressive visual, motor, or sensory changes or a single neurologic deficit may warrant referral to neurology and/or neuroimaging.


 

References

Biologic agents have provided patients with moderate to severe psoriasis with treatment alternatives that have improved systemic safety profiles and disease control1; however, case reports of associated neurologic complications have been emerging. Tumor necrosis factor α (TNF-α) inhibitors have been associated with central and peripheral demyelinating disorders. Notably, efalizumab was withdrawn from the market for its association with fatal cases of progressive multifocal leukoencephalopathy (PML).2,3 It is imperative for dermatologists to be familiar with the clinical presentation, evaluation, and diagnostic criteria of neurologic complications of biologic agents used in the treatment of psoriasis.

Leukoencephalopathy

Progressive multifocal leukoencephalopathy is a fatal demyelinating neurodegenerative disease caused by reactivation of the ubiquitous John Cunningham virus. Primary asymptomatic infection is thought to occur during childhood, then the virus remains latent. Reactivation usually occurs during severe immunosuppression and is classically described in human immunodeficiency virus infection, lymphoproliferative disorders, and other forms of cancer.4 A summary of PML and its association with biologics is found in Table 1.5-13 Few case reports of TNF-α inhibitor–associated PML exist, mostly in the presence of confounding factors such as immunosuppression or underlying autoimmune disease.10-13 Presenting symptoms of PML often are subacute, rapidly progressive, and can be focal or multifocal and include motor, cognitive, and visual deficits. Of note, there are 2 reported cases of ustekinumab associated with reversible posterior leukoencephalopathy syndrome, which is a hypertensive encephalopathy characterized by headache, altered mental status, vision abnormalities, and seizures.14,15 Fortunately, this disease is reversible with blood pressure control and removal of the immunosuppressive agent.16

Demyelinating Disorders

Clinical presentation of demyelinating events associated with biologic agents are varied but include optic neuritis, multiple sclerosis, transverse myelitis, and Guillain-Barré syndrome, among others.17-28 These demyelinating disorders with their salient features and associated biologics are summarized in Table 2.17-20,22-28 Patients on biologic agents, especially TNF-α inhibitors, with new-onset visual, motor, or sensory changes warrant closer inspection. Currently, there are no data on any neurologic side effects occurring with the new biologic secukinumab.29

Conclusion

Biologic agents are effective in treating moderate to severe plaque psoriasis, but awareness of associated neurological adverse effects, though rare, is important to consider. Physicians need to be able to counsel patients concerning these risks and promote informed decision-making prior to initiating biologics. Patients with a personal or strong family history of demyelinating disease should be considered for alternative treatment options before initiating anti–TNF-α therapy. Since the withdrawal of efalizumab, no new cases of PML have been reported in patients who were previously on a long-term course. Dermatologists should be vigilant in detecting signs of neurological complications so that an expedited evaluation and neurology referral may prevent progression of disease.

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